I propose to extend my investigations of the role of natural and imposed electrical currents in stimulating limb regeneration in amphibians (see Borgens et al., 1979, BioScience 29:468). I propose an investigation that consists largely of 3 broad areas: (1) To investigate the electrical fields and currents (generated by the skin) that traverse amputated amphibian forelimbs. I will carry out this study on regenerating species (urodeles), partially regenerating (certain species of anurans), and nonregenerating forms (particularly Ranids). In addition, I will study the electrical character of larval frog stumps as they progress through metamorphosis, losing the regenerative ability. (2) To modify these stump currents by a variety of means and to observe the responses. Endogenous stump currents can be manipulated by: implanted battery systems; enhancing or reducing the skin's natural ability to generate these stump currents; and by shunting or blocking the stump currents by mechanical means such that density of current traversing the stumps of urodeles is much reduced. In both (1) and (2), electrical measurements will be carried out with an ultrasensitive vibrating probe for the measurement of extracellular current (Jaffe and Nuccitelli, 1974, J. Cell Biol 63:614). (3) Using a variety of histological procedures I will characterize those cells which respond to the natural and applied fields. In particular, I will focus on nerve and the apical epithelium or wound epidermis. In general, I propose to gain an understanding of the way ionic currents initiate regeneration in amphibia and learn ways to manipulate this regeneration. I ultimately hope that this understanding will generate new insights into nerve regeneration and wound healing.